DESCRIPTION: In the United States in 1995, there were about 26,000 new cases of cancer of the ovary, and approximately 14,500 women died from it, making it the most lethal of the gynecological malignancies. Over the lifetime, close to 2 percent of women are affected. Ovarian cancer is difficult to treat because it is typically asymptomatic until advanced stages, and patients frequently present late in the disease course. The established risk factors do not clearly account for a large fraction of disease incidence, and the possible ovulatory or hormonal mechanisms by which these factors affect risk of developing ovarian cancer are not well understood. The application suggests a new hormonal hypothesis regarding the aetiology of ovarian cancer, and demonstrates a substantial body of pathologic, endocrinologic and epidemiologic evidence in support of this hypothesis. A population-based, case-control study to examine this hypothesis is proposed to be conducted in the State of Connecticut. The study will examine a collection of factors related to hormonal expression during and after the reproductive years. In total, about 500 non-mucinous and 80 mucinous ovarian-cancer cases, aged 35-79 years, will be identified prospectively in the state through the Rapid Case Ascertainment Shared Resource of the Yale Cancer Center. Approximately 1,000 randomly-selected population controls will be frequency-matched to the cases in three age groups. Controls will be identified using random-digit dialing for those under 65 years of age, and randomly chosen from rosters, provided by the Health Care Financing Administration for those 65 years and over. All of the subjects will be interviewed at home by trained interviewers, using a standardized, structured questionnaire which will include medical and reproductive history, and approximations of the various hormone-related factors. Univariate and multivariate analyses will be used to estimate relative risks for comparison of the cases with the controls. In general, the hormonal factors to be examined have received only a little attention with respect to ovarian cancer, and the proposed study will be the first to evaluate them systematically in a rigorous, large-scale study which will integrate all of the factors within a coherent aetiologic framework.